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Epidemiology and Etiology

In this series, the incidence of ALA was 8.5 patients/100,000 hospital admissions. Of those diagnosed, 75% were young men born outside the United States, and only 18% of patients were older than 50. We segregated ALAs by etiology (Table 1). The median time to presentation after travel was 20 weeks, with a range of 2 to 60 weeks. One third of all patients with ALA had associated medical conditions. Eight had tuberculosis, three had syphilis, three had hepatitis C, three had peptic ulcer disease, one had diabetes mellitus, and one had had a posttraumatic splenectomy. In addition, 43% of the patients studied had a history of heavy alcohol consumption.

TABLE 1. — Epidemiological Features in 56 Patients with ALA *

Features^	Endemic (En-ALA)	Travel (Tr-ALA)	No risk factors (N-ALA)
Number	27	13	16
Age, y !	28 (19-70)	40 (23-67)	36 (1-52)
Female:Male	5:22	0:13	2:14
Born in USA (%)	0 (0%)	3(23)	13(81)
Symptoms РТА, d$	9(1-120)	28 (2-180)	14(3-60)
Symptoms > 1 mo (%)	8 (30%)	7 (54%)	2(13%)
Hospitalization, d,	7(3-19)	8(3-18)	8 (3-38)
Defervescence, d	2(1-9)	3(1-7)	3 0-9)
Ethanol (%)§	11(41)	9(69)	4(25)
HIV positive (%)	0(0)	0(0)	6(38)#
Malnutrition (%)ll	2 (7)	3(23)	2(13)
Tuberculosis (%)	3(11)	2(15)	3(19)
Immunosuppressed (%)^	5(19)	4(31)	10(63)**
Immunosuppressed and/or ethanol (%)	15(56)	9(69)	12(75)

РТА = prior to admission

*Patients with En-ALA were born and had lived the majority of their lives in an endemic region and had been in the United States for less than one year. Patients with Tr-ALA were born in the USA or had lived the great majority of their lives in the USA and had traveled on one occasion to an endemic region. Patients with N-ALA were neither from nor had traveled to an endemic area.

! Numbers of patients in each group are shown, numbers in parentheses represent the percent of the total number in each specific subgroup (i.e. En-ALA, Tr-ALA and N-ALA), except where a range is shown.

$ Symptoms were any of those listed in Table 2.

§Heavy ethanol consumption was defined as > 150 grams ethanol/day.

ll Has evidence of wasting with severe hypoalbuminemia (<2.6 grams/dl) not due to any other cause (i.e. cardiac, liver, or renal failure).

^An immunosuppressed condition was considered to be present in patients with HIV infection, infection with Mycobacterium tuberculosis, or with malnutrition and hypoalbuminemia (albumin <2.6 g/dL) not due to other causes.

#P < 0,01 compared to either En-ALA or Tr-ALA. **P < 0.001 versus En-ALA group.

Patients with travel-related ALA were all men, many with histories of significant alcohol consumption. Tr-ALA patients were older than patients with En-ALA, and Tr-ALA presented subacutely in comparison with all other ALAs (Table 1). ALA was more prevalent in men than women in all groups. In the N-ALA group, there were six homosexual male patients, three of whom also used intravenous drugs. Three of these patients were known to be HIV-infected prior to admission, and three were diagnosed after their clinical presentation with ALA. Of note, the five HIV-infected patients who presented between 1990 and 1994 accounted for one third of all ALA cases during that time period. Other conditions associated with immunosuppression included tuberculosis, severe malnutrition with severe hypoalbuminemia (<2.6 g/dl) in the absence of other causes, splenectomy and diabetes (Table 1). The presence of HIV was significantly greater in patients with N-ALA than in other ALA groups (versus En-ALA P < 0.001; versus Tr-ALA P < 0.02). Similarly, the presence of an immunosuppressed state in patients with N-ALA was also significant (versus En-ALA and Tr-ALA patients, P < 0.01).

Clinical Features

Symptoms were generally nonspecific (Table 2), but a large proportion of patients presented with fever and pain in the right upper quadrant; both symptoms were present in 72% of patients. Physical signs reflected symptoms (Table 2). All afebrile patients exhibited an elevation in temperature during admission. Notably, 83% of all fevers were high grade. Defervescence occurred rapidly in most patients (median 2.5 days, range 1-9 days), except HIV-infected patients, whose fevers lasted three times longer than other patients’. Of all patients with ALA, 39% had anorexia, and 29% had weight loss. Only five patients reported bloody diarrhea. Jaundice was extremely rare. Buy Antibiotics

TABLE 2 – Symptoms and Signs at Presentation in 56 Patients with ALA

Finding	Number	%
Symptoms
Abdominal pain*	47	84
Fever	45	80
Chills	41	73
Nausea, vomiting and/or anorexia !	36	64
Sweats	32	57
Pleurisy, shortness of breath, and/or cough !!	23	41
Diarrhea § Weight loss ll	16 16	29 29
Signs
Fever ^	47	84
Abdominal tenderness	45	80
Hepatomegaly (>14 cm)	14	25
Respiratory findings #	14	25
Guarding or rebound	11	20
Jaundice	2	4

*Pain was located in the following areas: right sided (31), epigastric (7), diffuse (4) or not stated (5). Pain was referred to the following areas: back or flank (9), shoulder (7) and chest wall (2).

! There were 23, 22, and 18 patients with nausea, anorexia and vomiting, respectively. !! There were 13,8 and 8 patients with pleurisy, shortness of breath and cough, respec¬tively.

§ Bloody diarrhea was recorded in 5 patients.

II Median weight loss was 20 lb (range 5-40 1 b). There was a statistically significant dif¬ference for weight loss between ALA with an acute and chronic presentation (11 % versus 60%, respectively) with P < 0.0004 (Fisher's exact test). ^ There were 31 high grade (>38.5°C) and 16 low grade (37.5

# Respiratory findings included decreased breath sounds, dullness to percussion or added sounds.

The median duration of symptoms prior to presentation was relatively short, although 30% of patients had symptoms for at least 30 days. The majority of patients with En-ALA (63%) and N-ALA (82%) had a short duration of symptoms prior to admission (<14 days), and 90% were discharged within 2 weeks of admission. By contrast, Tr-ALA patients had an indolent course with more than 50% having symptoms lasting over 1 month prior to presentation (Table 1). The presentation of patients with En-ALA was notable for the presence of fever and abdominal tenderness (93%). Nausea (48%), vomiting (44%), and pleurisy (30%) were most frequently observed in patients with En-ALA. Of N-ALA patients, 88% had a significant history of fever and chills, and 93% had high-grade temperatures during admission. Only two thirds, however, reported a history of abdominal pain. On admission, Tr-ALA patients were least likely to be febrile or exhibit abdominal tenderness, but were most likely to display constitutional symptoms (80% sweats, 31% myalgias, 23% headaches), hepatomegaly (69%) and respiratory findings (40%). Hepatomegaly was found four and ten times more often in patients with a travel history than in patients with N-ALA or En-ALA, respectively. Moreover, constitutional symptoms (sweats, myalgias, headaches, P < .05) and hepatomegaly were more common in Tr-ALA than En-ALA (69% versus 7%, P < 0.0001), although abdominal tenderness was less frequent (62% versus 93%, P < .02).

Laboratory Findings

The white blood cell count (WBC) was elevated in 70% of patients (15 ± lX10^9/liter), and 10% had WBC > 20X10^9/liter). Serum liver tests were generally unremarkable and were as follows (mean + SEM): albumin 3.4 + 0.2 grams/dl (normal >3.3); total bilirubin 1.0 + 0.1 mg/dl (normal <1.2); alanine transaminase (ALT) 52+7 UAiter (normal <40); aspartate transaminase (AST) 44 + 8 U/liter (normal <50); alkaline phosphatase (SAP) 159 + 12 UAiter (normal <115). No patient had a bilirubin level >3.2 mg/dl, though 20% of patients had levels >1.2 mg/dl. Two fifths of patients had hypoalbuminemia with none having levels <1.9 grams/dl. One third had an underlying anemia (12.8 ± 0.3 grams/dl), but severe anemia was uncommon.

Imaging

Chest and abdominal plain films were nonspecific (Table 3). The sensitivities of computed tomography (CT) and ultrasonography (US) in detecting ALA were 100% and 85%, respectively (Table 3). The five ALAs missed by US were confirmed by two repeat USs, one CT, one surgery, and one autopsy. Amebic liver abcessess were most often single, located on the right posterior or anterior segment, and <10 cm in size (Table 4). Amebic liver abscessess on the left side were distributed equally between the lateral and medial segments. Of patients with Tr-ALA, 55% had ALAs >10 cm in size. This group accounted for the greatest proportion of multiple ALAs (40%) and ALAs involving the left or both lobes (40%). Patients with Tr-ALA or a chronic presentation were more likely to have an ALA >10 cm (Tr-ALA, 55% versus En-ALA, 22%, P < .01; chronic presentation, 47% versus acute presentation, 12%, P < 0.01) (Table 4). All six ALAs in HIV-infected patients were right-sided; five were located in the posterior segment. Canadian Pharmacy

TABLE 3 —Initial Radiographic Imaging in 56 Patients with ALA*

Features	Number
Abnormal chest x-ray !	21	44
Abnormal abdominal x-ray !!	17	52
Abnormal abdominal US §	47	90
<5.0 cm	14	25
5-10 cm	25	45
>10 cm	13	23
Abnormal abdominal CT scan	23	100

US = ultrasound and CT = computed tomography

* Available images included 48 chest X-rays, 33 plain abdominal films, 52 ultrasounds, 23 CT scans.

! There were 13 patients with a pleural effusion, 13 with elevated right hemidiaphragm, and 12 with atelectasis. Some studies had more than one abnormal finding.

!! There were 9 patients with a sentinel loop, 6 with air fluid levels, five with hepatomegaly and 1 with free air under the diaphragm. Some studies had more than one abnormal finding.

§ If multiple ALAs were present, then the largest was measured.

TABLE 4.—Location and Number of Amebic Abscesses

Feature	Number	%
Location of ALA
Right lobe	44	79
Left lobe	5	9
Both lobes (left, right, caudate)	5	9
Caudate	2	4
Number of ALA
Single	43	77
Multiple	13	23

ALAs were identified by ultrasound, computed tomography or autopsy.

Microbiology

Amebic serology was performed using the following tests: indirect hemagglutination (IHА) in 37 patients, enzyme-linked immunoabsorbent assay (ELISA) in 15 patients, counterimmunoelectrophoresis (CIE) in 14 patients, latex fixation (LF) in 8 patients, immunodiffusion (ID) in two patients, and complement-fixation (CF) in 1 patient. Of the 77 tests, 5 were initially negative, including 2 IHAs, 2 CIEs, and 1 LF. In 13 out of 43 patients (30%), cultures of stool specimens revealed cysts or trophozoites, either singly or in combination (50%, 37% and 23% in Tr-ALA, En-ALA and N-ALA patients, respectively). Trophozoites were identified in 4% of abscess aspirates. Abscess cultures from two patients grew one contaminant and an Escherichia coli. Blood cultures from three patients grew two contaminants and an Escherichia coli.

Treatment

All patients received antibiotic treatment: 75% received a combination of metronidazole and diiodoquinol, and 25% received metronidazole alone. Almost half the patients underwent invasive diagnostic or therapeutic procedures, of which percutaneous needle aspiration was the most commonly performed. Of 20 patients who underwent aspiration, 1 developed acute respiratory distress (ARDS). Patients in the N-ALA group were most likely to undergo an invasive procedure (>60%). Defervescence took longer in patients who underwent invasive procedures than in those treated with antibiotics alone (Table 5).
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Morbidity and Mortality

Complications included contiguous extension or rupture in 6 (11%) of patients, ARDS after an interventional radiological procedure in 1 (2%), recurrence in 2 (4%) and superinfection in 1 patient (2%). This latter patient, the only patient who died in this series, had Escherichia coli septicemia and multisystem organ failure with positive blood and abscess cultures. The diagnosis was not suspected prior to death and only made at autopsy. Patients with Tr-ALA (15%) and N-ALA (13%) were twice as likely as En-ALA (7%) patients to have a contiguous extension or rupture, but the latter had the only recorded death (4%). The recurrence rate was 0% for patients with N-ALA, 4% for patients with En-ALA, and 7% for patients with Tr-ALA. There was no consistent relationship between clinical improvement and a changed radiological appearance.